Reconstitution of IDUA activity in MPS I mice upon transplantation of wild-type or gene-corrected HSPCs. (A) Experimental scheme. Idua^−/− and Idua^+/+ cells were transduced with IDUA-LV or GFP-encoding LV (in which transgene expression was driven by the human phosphoglycerate kinase promoter) and then transplanted (1 × 10⁶ cells/mouse) into lethally irradiated mice, as indicated. GT, gene therapy–treated Idua^−/− mice; HCT, Idua^−/− mice transplanted with WT HSPC transduced with GFP-LV; MPS I, Idua^−/− mice transplanted with GFP-LV–transduced Idua^−/− HSPCs (mock-transplanted affected controls); WT, Idua^+/+ mice transplanted with GFP-LV–transduced Idua^+/+ HSPCs (mock-transplanted WT controls). (B-D) IDUA activity was measured in the PBMCs (B), in the serum (C), and in the tissues indicated below the x-axis (D) of mice transplanted with either mock-transduced or gene-corrected HSPCs at 4 weeks (B) or 6 months after transplant at sacrifice (B-D). Each dot represents one mouse, and average values are shown (black line). (E) Gene therapy–treated mice were divided into 2 groups according to the IDUA activity measured in total PBMCs (at 6 months from transplantation; left chart) and to the vector copy number per genome (VCN) measured on total BM cells (right chart). IDUA activity measured in the brain is shown for animals having IDUA activity in PBMCs below (<) or above (>) 1500 nmol/mg/h and carrying less (<) or more (>) than 5 LV copies per genome in the BM (1500 nmol/mg/h and 5 LV copies/genome are the average values measured in the entire pool of gene therapy–treated mice). Mean ± min/max are shown. **P < .01; ***P < .001 with Student t test.